Nucleic acid helicases are a large family of enzymes that unwind double-stranded DNA and RNA an use the energy derived from the hydrolysis of a nucleoside 5'-triphosphate (usually ATP) to drive the unwinding process. ATP-dependent DNA helicases are needed to provide single-stranded DNA for DNA replication, repair, recombination, and transcription. ATP-dependent RNA helicases are needed to provide single-stranded RNA for mRNA splicing, translation, and ribosomal assembly.
RNA helicases from a wide variety of sources including bacteria, yeast, and mammals share a number of highly conserved sequences and structural features suggesting that RNA helicase activity is of fundamental importance to cells of all types. For example, yeast Drs1 protein is involved in ribosomal RNA processing; yeast TIF1 and TIF2 and mammalian eIF-4A are essential to the initiation of RNA translatio; and human p68 antigen regulates cell growth and division (Ripmaster, T. L. et al. (1992) Proc. Natl. Acad. Sci. 89:11131-35; Chang, T-H et al. (1990) Proc. Natl. Acad. Sci. 87:1571-75). These RNA helicases demonstrate strong sequence homology over a stretch of some 420 amino acids. Included among these conserved sequences are the sequence DX.sub.4 A.sub.4 GKT (SEQ ID NO:5) typical for the A motif of an ATP binding protein, the "DEAD box" sequence (aspartate-glutamate-alanine-aspartate) (SEQ ID NO:6) associated with ATPase activity, the sequence SAT associated with the actual helicase unwinding region, and the sequence H/QRXGRXXR (SEQ ID NO:7 and SEQ ID NO:8) required for RNA binding and ATP hydrolysis (Pause, A. et al. (1993) Mol. Cell Biol. 13:6789-98). Moreover, these sequences are similarly spaced apart in members of the helicase family and most often found in the middle region of the protein. Differences outside of the conserved regions are believed to reflect differences in the functional roles of individual proteins (Chang et al., supra).
The discovery of a new ATP-dependent RNA helicase and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of cancer, neurological disorders, and immune disorders.